Chronic Myelomonocytic Leukemia

DLI is an effective treatment strategy for post-transplant relapse of all myeloid malignancies, with specific genetic subtypes showing poorer outcomes and survival.

The 1p36.2 chromosomal region harbors tumor suppressors such as PR domain containing 16 (PRDM16), Tumor Protein 73 (TP73), Cadherin 5 or VE-cadherin (CHD5), and Kinase Family Member 1B (KIF1B), while the 3p12 chromosomal location plays a role in the malignant transformation and disruption of the tumor suppressors, focusing on the genomic instability observed in the case. These changes may partially harbor the capacity to contribute to the pathogenesis of aggressive behaviors in leukemia through failure of apoptosis, chromatin remodeling pathways, and enhanced self-renewal capabilities of stem cells.

Median OS was 27.2 vs. 17.2 months in AML and 16.7 vs. 23.7 months in MDS/CMML for clearance versus persistence groups, respectively. These findings suggest that SF mutation clearance does not significantly impact OS but may influence other clinical outcomes in patients with myeloid neoplasms harboring SF mutations.

P2, N=25, Suspended, Abhay Singh, MD MPH | Recruiting --> Suspended

P1/2, N=34, Terminated, M.D. Anderson Cancer Center | Active, not recruiting --> Terminated; <75% participation

P=N/A, N=31, Recruiting, Peking University People's Hospital | Phase classification: P4 --> P=N/A

P2, N=20, Recruiting, University of Florida | Trial completion date: May 2027 --> May 2028 | Trial primary completion date: May 2026 --> May 2027

We describe a 60-year-old man with FLT3-ITD-mutated acute myeloid leukemia (AML) who achieved durable remission following venetoclax-based therapy and a combined HLA-matched sibling HCT-kidney transplant with FLT3 inhibitor maintenance. Four years post-transplant, he developed chronic myelomonocytic leukemia (CMML-1) characterized by re-emergence of driver mutations without FLT3-ITD, marked loss of donor myeloid chimerism, preserved donor T-cell chimerism, and sustained renal allograft function. This case highlights a unique clinical circumstance that may function to recontextualize myelomonocytic features in AML: that they can be attributed to acute leukemias arising from clonal hematopoiesis or occult chronic malignancies, as opposed to de novo AML, particularly given the difficulty in differentiating the two in the acute leukemic setting.

In patient-derived xenograft models of PTPN11-mutant JMML, dual NLRP3/PTGS2 inhibition combined with MEK blockade most effectively reduced leukemic burden, decreased human CD45⁺ engraftment, and depleted leukemic CD34⁺CD38⁺ progenitors and GMPs while restoring MEP populations, resulting in significantly improved overall survival. Together, these findings establish IL-17A/PTGS2/NLRP3 signaling as a central driver of immune suppression and myeloid expansion in PTPN11-mutant JMML and highlight combinatorial anti-inflammatory targeting as a promising therapeutic strategy for this high-risk disease.

Although O-CMML may be a unique entity, the current classification does not enrich CMML-like variants by all clinical measures. A comprehensive analysis of clinical, molecular and immunophenotype is needed for better classification.

P2, N=20, Active, not recruiting, City of Hope Medical Center | Trial completion date: May 2026 --> Mar 2027 | Trial primary completion date: May 2026 --> Mar 2027

Although the course is most often self-limiting, justifying an initial conservative approach, certain extensive forms may require systemic treatment. The dermatologist plays a central role in diagnosis, based on a combination of clinical, dermoscopic, histopathological, and immunohistochemical findings, and in the multidisciplinary decision-making regarding treatment.